Dag Nordhaug

Norwegian University of Science and Technology, Trondheim, Sor-Trondelag Fylke, Norway

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Publications (24)55.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Since few studies have presented a thorough analysis of the effect of levosimendan (LEV) on contractility, our purpose was to investigate in vivo cardiac function as well as in vitro cardiomyocyte function and calcium (Ca(2+) ) handling following LEV treatment. Rats with post-myocardial infarction heart failure (HF) induced by ligation of the left anterior descending coronary artery and sham-operated animals were randomized to infusion of LEV (2.4 μg∙ kg(-1) ∙ min(-1) ) or vehicle for 40 min. Echocardiographic examination was coupled to pressure-volume sampling in the left ventricle before (B) and after (40 min) infusion. Isolated left ventricular cardiomyocytes were studied in an epifluorescence microscope. HF LEV (n=6), HF vehicle (n=7), sham LEV (n=5) and sham vehicle (n=6) animals were included. LEV infusion compared to vehicle in HF animals reduced left ventricular end-diastolic pressure and mean arterial pressure (both P<0.001) and improved the slope of the preload-recruitable stroke work (P<0.05). Administrating LEV to HF cardiomyocytes in vitro improved fractional shortening and Ca(2+) sensitivity index ratio, and increased the diastolic Ca(2+) (all P<0.01). In HF animals LEV improved the contractility by increasing the Ca(2+) sensitivity. Furthermore loading conditions were changed, and LEV could consequently change organ perfusion. An observed increase in diastolic Ca(2+) following LEV treatment and clinical implications of this should be further addressed. This article is protected by copyright. All rights reserved.
    Acta Physiologica 02/2014; · 4.38 Impact Factor
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    ABSTRACT: Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1-4 (D1-D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P = 0.219), 46 (P = 0.067) and 41 (P = 0.267) at D1-D4), although the more load-dependent contractility indicator of dP/dt(max) was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA-MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2011; 41(6):1377-83. · 2.40 Impact Factor
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    ABSTRACT: Competitive flow from native coronary vessels is considered a major factor in the failure of coronary bypass grafts. However, the pathophysiological effects are not fully understood. Low and oscillatory wall shear stress (WSS) is known to induce endothelial dysfunction and vascular disease, like atherosclerosis and intimal hyperplasia. The aim was to investigate the impact of competitive flow on WSS in mammary artery bypass grafts. Using computational fluid dynamics, WSS was calculated in a left internal mammary artery (LIMA) graft to the left anterior descending artery in a three-dimensional in vivo porcine coronary artery bypass graft model. The following conditions were investigated: high competitive flow (non-significant coronary lesion), partial competitive flow (significant coronary lesion), and no competitive flow (totally occluded coronary vessel). Time-averaged WSS of LIMA at high, partial, and no competitive flow were 0.3-0.6, 0.6-3.0, and 0.9-3.0 Pa, respectively. Further, oscillatory WSS quantified as the oscillatory shear index (OSI) ranged from (maximum OSI = 0.5 equals zero net WSS) 0.15 to 0.35, <0.05, and <0.05, respectively. Thus, high competitive flow resulted in substantial oscillatory and low WSS. Moderate competitive flow resulted in WSS and OSI similar to the no competitive flow condition. Graft flow is highly dependent on the degree of competitive flow. High competitive flow was found to produce unfavourable WSS consistent with endothelial dysfunction and subsequent graft narrowing and failure. Partial competitive flow, however, may be better tolerated as it was found to be similar to the ideal condition of no competitive flow.
    Cardiovascular research 12/2010; 88(3):512-9. · 5.81 Impact Factor
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    ABSTRACT: Freedom Solo is a stentless biological aortic valve which is implanted supra-annularly with a single suture line. An increased risk of postoperative thrombocytopenia in the early postoperative period has been reported in recent studies. In our study we evaluated postoperative haemodynamic performance and thrombocyte-levels. Thirty seven patients who underwent valve implantation of the Sorin Freedom Solo stentless valve were included. The haemodynamic performance of the valve was evaluated by transthoracic echocardiography postoperatively at the fourth day (mean) and after a median of 4.2 months. The mean gradient (mmHg) of Freedom Solo was 7.5 at four days and 8.6 at 4.2 months. Postoperatively no patient had more than grade 1 leakage. Seven percent of the patients had a reduction of thrombocytes to less than 20% of the preoperative level. Seventy six percent had a minimum postoperative thrombocyte level less than 100*10(9)/L. The 30 days mortality in our patient material was zero. Implantation of the Freedom Solo valve was uncomplicated in our experience. Favourable transvalvular gradients and no significant leaks were found. In accordance with the literature, we found a high percentage of patients having a postoperative level of thrombocytes less than 100*10(9)/L after implantation of Freedom Solo.
    Scandinavian cardiovascular journal: SCJ 10/2010; 44(5):301-6. · 1.07 Impact Factor
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    ABSTRACT: Levosimendan is a calcium-sensitising inotropic agent and a vasodilator used in the treatment of heart failure. Post-cardiotomy cardiac failure is more common in patients with a low preoperative left ventricular ejection fraction (LVEF). We aim at investigating how prophylactic treatment with levosimendan before weaning from cardiopulmonary bypass (CPB) affects postoperative haemodynamics and outcome in patients with low preoperative LVEF. Patients with a preoperative LVEF < or =30% treated with levosimendan before weaning from CPB were included in the study. Each patient was matched to a control patient with respect to the following criteria: surgical procedure, EuroSCORE, age, gender and the use of intra-aortic balloon pump. We investigated postoperative haemodynamics in the intensive care unit (ICU) at time points: 1, arrival; 2, approximately 7h after arrival; and 3, the first postoperative morning. In addition, mortality was evaluated. Thirty patients treated with levosimendan and 30 matched controls were enrolled in the study. No statistically significant differences in cardiac index (CI) (l min(-1)m(-2)), stroke volume index (SVI) (mlm(-2)), mixed venous O(2)-saturation (SvO(2)) (%) or heart rate (HR) (beats per minute) between the two groups measured at the three time points 1-3 were registered. Mean arterial blood pressure (MAP) (mmHg) was lower in the levosimendan group both at time points 2 (68, range: 65-71 vs 75, range: 72-78; p=0.009) and 3 (72, range: 69-74 vs 78, range: 74-82; p=0.01), despite a higher dose of norepinephrine in the treatment group (p=0.021). A significantly higher number of control patients were treated with classic adrenergic inotropes both in the operating room (p=0.013) and in the ICU (p<0.001). Thirty days mortality was the same in both groups (7%). Prophylactic infusion of levosimendan initiated before weaning from CPB did not lead to superior haemodynamic parameters (CI, SVI, SvO(2)) compared to controls. Levosimendan reduced MAP and increased the need for norepinephrine postoperatively.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 07/2009; 36(6):1024-30. · 2.40 Impact Factor
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    ABSTRACT: To assess whether coronary graft flow patterns are affected differently by native coronary competitive flow or by stenosis of the coronary anastomosis. Nine pigs (65-70 kg) underwent off-pump grafting of the left internal mammary artery to the left anterior descending artery (LAD). Transit-time flow patterns in the mammary grafts were recorded under four different conditions: (1) baseline flow (proximal LAD occluded), (2) full competitive flow, (3) partial competitive flow and (4) after creation of a stenosis in the anastomosis. Competitive flow was achieved by an adjustable occluder on the left anterior descending artery. The mean luminal stenosis of the anastomosis was 75+/-11%, calculated by epicardial ultrasound. Mean flow, systolic and diastolic antegrade and retrograde flow during different flow conditions were calculated as ratios of baseline flow and compared. Different derived flow indexes were calculated and compared in the same manner. Friedman's test and post hoc analyses by Wilcoxon signed-ranks were performed without correction for multiple comparisons. Mean graft flow was more reduced by competitive flow than by a stenotic anastomosis of 75+/-11%. Competitive flow significantly decreased diastolic antegrade flow and both diastolic and systolic maximum peak flows, but increased retrograde flow, compared with baseline and stenosis. Furthermore, competitive flow and stenosis could be distinguished by analysis of several derived indexes. Pulsatility index (maximum-minimum flow/mean flow) and insufficiency percent (retrograde flow as fraction of total flow) was increased significantly more by competitive flow than by stenosis. Diastolic filling percent was significantly reduced at competitive flow compared with stenosis and baseline. The mammary graft flow was significantly reduced by native coronary competitive flow, but marginally decreased by a stenotic anastomosis of 75% mean luminal stenosis. Reduction of graft flow due to competition was particularly evident in diastole. A detailed flow pattern analysis may differentiate between competitive flow and stenosis of the anastomosis.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2009; 36(1):137-42; discussion 142. · 2.40 Impact Factor
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    ABSTRACT: The purpose of this study was to establish patient characteristics and the severity and extent of thoracic injury for patients referred to a Norwegian regional trauma centre. All patients (n = 436) treated for thoracic injuries at St. Olavs University Hospital between 01.01. 2003 and 31.12. 2004 were analysed retrospectively. The patients were identified from the hospital diagnosis registry by ICD-10 codes. Traffic accidents and falls accounted for 92% of all injuries. The most common thoracic injury was rib fracture (55%) and the most common internal thoracic injury was pneumothorax (24%). About half of the patients (221/446) had associated extra-thoracic injuries. Observation and pain relief was the only treatment in 290 patients. Chest tube was the most common treatment, and was used in 88 cases (20%). 50 patients (12%) received ventilator treatment. Nine patients underwent thoracic surgery, four of these died. In-hospital mortality was 5% (20/436 patients). Head injury and bleeding from internal organs were the most frequent causes of death. Thoracic injuries are a frequent challenge at St. Olavs University Hospital. Many patients have both thoracic and extra-thoracic injuries. Mortality is related to the severity of the injury, advanced age and comorbidity.
    Tidsskrift for den Norske laegeforening 06/2007; 127(11):1496-9.
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    ABSTRACT: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload. Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm. Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways). We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.
    European Journal of Cardio-Thoracic Surgery 05/2007; 31(4):677-84. · 2.67 Impact Factor
  • Alexander Wahba, Dag Nordhaug
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    ABSTRACT: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was what the long-term results of cardiac valve replacements are in left sided endocarditis with a history of i.v. drug abuse? A total of 286 publications were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patients group studied, study type, relevant outcomes, results, and study weaknesses of these papers were tabulated. We conclude that cardiac valve replacement for left sided endocarditis in i.v. drug users carries a substantial mortality. Continued drug abuse is the commonest cause of death in this patient group. In contrast, the type of valve used to perform the replacement does not seem to influence mortality. Postoperative management should focus on treatment of the drug addiction.
    Interactive Cardiovascular and Thoracic Surgery 11/2006; 5(5):608-10. · 1.11 Impact Factor
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    ABSTRACT: Our previous studies indicate that left ventricular end-systolic pressure-volume relations (ESPVRs) or elastance (Ees) are not reduced in studies where expected reductions of contractility should be found (i.e., heart failure, stunning, and endotoxemia). The present study was done to assess whether this phenomenon is due to a particular load sensitivity of elastance, rendering this index inappropriate as a measurement of contractility in pathologic states in vivo. METHODS AND RESULTS: Analysis of previously generated data revealed an increased ESPVR in stunned hearts, in pigs made endotoxemic, and in hearts rapidly paced. After inducing acute heart failure by microembolization, the ESPVR was increased when assessed using linear relations but reduced when assessing ESPVR by a curvilinear algorithm. To further evaluate the effect of different load alterations on ESPVR, this relation was generated by (i) inferior vena caval occlusions (VCOs); (ii) gradually occluding the descending aorta (pressure interventions); and (iii) rapidly infusing blood (120 mL) into the left atrium (volume increments). The load protocol was applied in 5 pigs, before and after the left ventricle was stunned by 11 brief left main coronary artery occlusions/reperfusions (accumulated ischemia 20 min affecting 81% of the left ventricle). Correlation coefficients for left ventricular elastance ranged from 0.93 to 0.99 in all the 3 types of loading interventions. Despite significant reductions in stroke volume, stroke work, and dP/dtmax, VCO-calculated linear and curvilinear Ees increased 90 min after stunning (55% +/- 4% and 94% +/- 6%, respectively). Linear Ees during pressure interventions decreased 36% +/- 1%, whereas curvilinear Ees decreased 33% +/- 3%. During volume infusions, linear Ees decreased 27% +/- 2%. We achieved the same results after blocking the baroreceptor reflexes using hexamethonium. CONCLUSIONS: The Ees is particularly load dependent and will reflect load interventions more than the inotropic state of the cardiac muscle. A VCO-generated Ees increase could be an unmasking of a pronounced preload sensitivity in failing myocardium.
    Shock 05/2006; 25(4):370-6. · 2.61 Impact Factor
  • European Journal of Heart Failure Supplements 06/2005; 4(S1).
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    ABSTRACT: The time constant of mechanical restitution (T(MRC)), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure. In this study, we tested the hypothesis that T(MRC) also can identify post-ischemic, reversible LV dysfunction (stunning). Stunning was induced by a series of left main coronary artery occlusions in eight anesthetized open chest pigs. Left ventricular pressure-volume relations were assessed using a pressure-volume catheter during right atrial pacing. Mechanical restitution curves (MRCs) were constructed using two different measures of contractile response: maximal first derivative of pressure (CR(dP/dtmax)) and stroke work (CR(SW)). Mean arterial pressure, stroke volume and dP/dtmax were decreased 30 min after stunning. Slopes of end-systolic pressure volume relation and preload recruitable stroke work, however, showed no significant changes after stunning. For MRCs based on CR(dP/dtmax), T(MRC) increased in all eight animals. Using CR(SW), T(MRC) increased in seven out of eight pigs. Ischemia-reperfusion induce changes in MRCs based on CR(dP/dtmax), and CR(SW). The MRC concept may have potential as a clinical left ventricular performance index.
    Scandinavian Cardiovascular Journal 05/2005; 39(1-2):107-14. · 0.82 Impact Factor
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    ABSTRACT: The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.
    European Journal of Heart Failure 11/2004; 6(6):705-13. · 5.25 Impact Factor
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    ABSTRACT: Left ventricular unloading has a potentially deleterious effect in right ventricular failure as a result of altered septal interplay. However, a positive effect of an intraaortic balloon pump during right ventricular failure has been suggested. We investigated the impact of intraaortic balloon pumping on hemodynamics and both left and right ventricular function in an experimental model of isolated right ventricular failure. Sixteen anesthetized pigs (25 to 34 kg) were used in an in vivo model. Pressure-conductance catheters assessed right and left ventricular pressure-volume relationships. Acute right ventricular failure was induced by right coronary microembolization, and led to severely impaired right ventricular function, reduced cardiac output and arterial pressure, and an increased pulmonary vascular resistance and pulmonary arterial elastance. Animals were then randomized to balloon pump or control groups and evaluated with respect to hemodynamics and ventricular function after 1 hour. Intraaortic balloon pumping did not alter right or left ventricular contractility. However, balloon pump-treated animals had significantly improved cardiac output (+18% +/- 18% versus -6% +/- 7%; p = 0.003) and mean arterial pressure (+36% +/- 30% versus -7% +/- 14%; p = 0.004) compared with controls. Animals in the balloon pump group had lower pulmonary vascular resistance (795 +/- 63 versus 912 +/- 259 dynes . sec . cm(-5); p < 0.01) and pulmonary arterial elastance (1.14 +/- 0.20 versus 1.69 +/- 0.65 mm Hg/mL; p < 0.01), and increased stroke volume (22.3 +/- 4.7 versus 17.9 +/- 4.7 mL; p = 0.016). Right ventricular efficiency was also improved in the balloon pump group (stroke work per pressure-volume area = 0.60 +/- 0.14 versus 0.41 +/- 0.12; p < 0.01). Intraaortic balloon pump support does not alter right or left ventricular function in acute right ventricular failure. However, arterial pressure, cardiac output, and right ventricular efficiency are improved, possibly because of a balloon pump-induced reduction in pulmonary arterial resistance.
    The Annals of thoracic surgery 10/2004; 78(4):1426-32. · 3.45 Impact Factor
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    ABSTRACT: Myocardial oxygen consumption (MVO2) in the septic myocardium is increased despite reduced left ventricular mechanical work. We investigated the mechanism behind this energetic inefficiency in the septic myocardium. To clarify whether energy consumption in basal metabolism or excitation-contraction (EC) coupling is elevated in the septic myocardium, we separated MVO2 used for these two processes. We assessed hemodynamics, left ventricular pressure-volume area, left ventricular MVO2, myocardial substrate metabolism and the inflammatory response in eight control pigs and in eight septic pigs receiving E. coli endotoxin. Using cardiopulmonary bypass (CPB), unloaded MVO2 was assessed before and after arrest of electromechanical activity using KCl infusions. Unloaded MVO2 was significantly higher in the septic group compared to the control group (65.7 +/- 12.9 vs. 43.3 +/- 15.1 J.min(-1).100 g LV(-1), p < 0.005), but basal MVO2 after 5 min KCl arrest was equal in the two groups. No difference in mechanical energy consumption or substrate metabolism was observed between groups. Basal MVO2 in the septic myocardium is not elevated, but an increased MVO2 for EC coupling is responsible for the energetic inefficiency.
    Cardiovascular Research 08/2004; 63(2):256-63. · 5.81 Impact Factor
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    ABSTRACT: Myocardial oxygen consumption (MVO) in the septic myocardium is comparatively high in relation to the sepsis-induced reduction in ventricular work. Our previous studies indicate that this energetic inefficiency is due to increased energy consumption in excitation-contraction (EC) coupling, i.e. myocardial calcium handling. To further confirm this observation, we assessed the oxygen cost of contractility in anesthetized pigs before and 2 h after induction of endotoxemia (1 microg/kg endotoxin infusion over 1 h, Escherichia coli toxin, n=6). Baroreceptor reflexes were blocked by hexamethonium. Contractility was increased by stepwise dopamine infusions at baseline and 2 h after induction of endotoxemia. Oxygen cost of contractility was assessed as the relationship between myocardial contractility (E or elastance) and non-mechanical oxygen consumption (unloaded MVO), a measure of energy consumption in EC coupling or calcium handling. Non-mechanical oxygen consumption (unloaded MVO) was higher after endotoxin infusions than at baseline (0.641 +/- 0.05 vs 0.383 +/- 0.07 J/beat/100 g, p < 0.05). The relationship between unloaded MVO and E, constructed by the dopamine response, was highly linear both at baseline and endotoxemia (r2 =0.76-0.99). However, endotoxin increased oxygen cost of contractility by approximately 45% (baseline 0.06 +/- 0.03 vs endotoxin 0.09 +/- 0.04 J ml/mmHg/beat/100 g). Acute endotoxemia increases oxygen cost of contractility, a measure of energy consumed in EC coupling or myocardial calcium handling.
    Scandinavian Cardiovascular Journal 06/2004; 38(3):187-92. · 0.82 Impact Factor
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    ABSTRACT: To determine whether the adenosine triphosphate-sensitive potassium channel opener nicorandil, instead of potassium in cold crystalloid cardioplegia, may enhance cardioprotection, crystalloid cardioplegia with nicorandil, magnesium, and procaine was compared with standard crystalloid cardioplegia in terms of left ventricular performance and efficiency. Sixteen pigs were randomly assigned to receive cold hyperkalemic crystalloid cardioplegia (n = 8) or nicorandil in cold saline (n = 8). Cold (4 degrees C) cardioplegic solutions were given antegradely and intermittently, with a cross-clamp time of 60 minutes. The preload recruitable stroke work relationship (PRSW), pressure-volume area (PVA), and myocardial oxygen consumption (MVO(2)) were calculated at baseline and at one and two hours following cross-clamp release, using combined pressure-volume conductance catheters, coronary flow probes, and O(2)-content differences. The left ventricular contractility expressed in PRSW was reduced to 58% (standard deviation [SD]: 20) of baseline in the crystalloid group and to 89% (SD: 20) in the nicorandil group two hours after cross-clamp release (p = 0.044). The slope of the MVO(2)-PVA relationship increased in the crystalloid group from 1.59 (SD: 0.22) before cardioplegia to 2.55 (SD: 0.73) afterwards, significantly more than in the nicorandil group, where the slope changed from 1.69 (SD: 0.30) to 1.95 (SD: 0.47) (p = 0.027). Nicorandil in a crystalloid cardioplegic solution was easily employed and contractility was significantly better than after standard hyperkalemic cardioplegia. The smaller shift of the slope in the MVO(2)-PVA relationship in the nicorandil group shows improved efficiency in oxygen to mechanical transfer compared with the crystalloid group.
    The Annals of Thoracic Surgery 05/2004; 77(4):1391-7. · 3.45 Impact Factor
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    ABSTRACT: Myocardial dysfunction is believed to be a central part of septic multiorgan manifestations. The aim of the present study was to assess whether E. coli sepsis in an in vivo model would induce a dysfunction in the relationship between mechanical work and energy consumption in the left ventricle (LV). Accordingly, we measured hemodynamics, left ventricular pressure-volume area (PVA), and myocardial oxygen consumption (MVo2) in deeply anesthetized pigs. Eight pigs received 2.0 +/- 0.5 x 10(9) E. coli bacteria intravenously, and seven served as controls. Compared with baseline and the control group, no alternations were observed in LV diastolic function or indices of contractility in the septic group. The MVo2-PVA relationship was highly linear in both groups (all r2 = 0.96-0.99). At 5 h, the y-axis intercept of the MVo2-PVA relationship (nonmechanical MVo2) had increased in the sepsis group by 70% compared with baseline (P = 0.004) and by 60% compared with the control group (P = 0.003). Contractile efficiency (the inverse of the MVo2-PVA slope) remained unchanged over time and between groups. The study demonstrates a profound increase in nonmechanical oxygen consumption during E. coli sepsis in the LV.
    Shock 03/2004; 21(2):103-9. · 2.61 Impact Factor
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    ABSTRACT: The ATP-sensitive potassium channel (K(ATP)) activator nicorandil used as cardioplegic agent may protect the left ventricle during cardiac arrest. Nicorandil in cold blood was compared with standard hyperkalemic blood and crystalloid cardioplegia. Twenty-one pigs were randomly assigned to three groups: (1) cold hyperkalemic crystalloid (n=7); (2) cold hyperkalemic blood (n=7); and (3) nicorandil as cardioplegia in cold blood (n=7). Left ventricular mechanical performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were measured before and at 1 and at 2 h after 60 min of cold global ischemia on cardiopulmonary bypass using intraventricular pressure-volume conductance catheters, coronary flow probes and O(2)-content difference. The slope (M(w)) of the stroke work end-diastolic volume relationship, the preload recriutable stroke work relationship, was unchanged after ischemia in the nicorandil group, but was reduced to averaged 62.5% (standard deviation 14) of baseline values in both hyperkalemic perfusions (P<0.05). The slope of the MVO(2)-PVA relationship was unchanged after nicorandil cardioplegia while the slope after hyperkalemic blood and crystalloid cardioplegia increased with 33% (P<0.02) and 52% (P<0.02) of baseline values, respectively. Nicorandil as sole cardioplegic agent in cold blood given intermittently preserves left ventricular contractility and myocardial energetics significantly better than traditional forms of cardioplegia after cardiac arrest.
    European Journal of Cardio-Thoracic Surgery 06/2003; 23(5):670-7. · 2.67 Impact Factor
  • European Journal of Heart Failure Supplements 01/2003; 2(1).

Publication Stats

113 Citations
55.90 Total Impact Points

Institutions

  • 2011
    • Norwegian University of Science and Technology
      • Department of Circulation and Medical Imaging
      Trondheim, Sor-Trondelag Fylke, Norway
  • 2006–2007
    • St. Olavs Hospital
      Nidaros, Sør-Trøndelag, Norway
  • 2002–2007
    • University Hospital of North Norway
      Tromsø, Troms, Norway
  • 2002–2006
    • Universitetet i Tromsø
      • Department of Clinical Medicine (IKM)
      Tromsø, Troms Fylke, Norway